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Effect of Preeclampsia on Placental Function: Influence of Sexual Dimorphism, microRNA’s and Mitochondria

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Advances in Fetal and Neonatal Physiology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 814))

Abstract

In pregnancy fetal growth and development occur in a sexually dimorphic manner. Male and female fetuses respond differently to the intrauterine environment with males disproportionately suffering from perinatal morbidity and mortality. We have demonstrated placental dysfunction and sexually dimorphic responses in pregnancies complicated by severe preeclampsia. Production of cytokines and apoptosis in the male placenta is heightened relative to that of the female placenta. We also find increased expression and stabilization and a sexual dimorphism in expression of the transcription factor HIF-1α, but a defect in binding to the hypoxia response element with corresponding reduced expression of HIF-1α target genes including VEGF and Glut-1. HIF-1α is involved in crosstalk with the redox sensitive transcription factor NFκB in regulation by cytokines, reactive oxygen species and expression of inflammatory genes. We find increased placental expression and DNA binding of NFκB and a sexually dimorphic response suggesting a role for NFκB in placental dysfunction with preeclampsia. Placental mitochondrial complex III activity and complex I and IV expression are reduced and alterations in mitochondrial morphology are found in preeclampsia and are linked to the hypoxamir miR-210. We propose that with severe PE placental HIF-1α is stabilized by excessive ROS, inflammation and relative hypoxia. This increases the expression of miR-210 in the placenta causing repression of mitochondria-associated target genes, potentially leading to mitochondrial and placental dysfunction. This placental dysfunction may lead to a fetal programming effect that results in disease in later life.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229-3900, USA

    Leslie Myatt, Sribalasubashini Muralimanoharan & Alina Maloyan

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  2. Sribalasubashini Muralimanoharan
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  3. Alina Maloyan
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Correspondence to Leslie Myatt .

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Editors and Affiliations

  1. Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Lubo Zhang

  2. Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Charles A. Ducsay

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© 2014 Springer Science+Business Media New York

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Myatt, L., Muralimanoharan, S., Maloyan, A. (2014). Effect of Preeclampsia on Placental Function: Influence of Sexual Dimorphism, microRNA’s and Mitochondria. In: Zhang, L., Ducsay, C. (eds) Advances in Fetal and Neonatal Physiology. Advances in Experimental Medicine and Biology, vol 814. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1031-1_12

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